Irbesartan is a known angiotensin II receptor antagonist, the octapeptide produced by the action of the angiotensin converting enzyme and having considerable influence on blood pressure. The structure of Irbesartan is shown in (I).

The synthesis of Irbesartan has been described in U.S. Pat. No. 5,270,317 and U.S. Pat. No. 5,559,233, among others. The antepenultimate reaction step consists in the reaction of a cyano group in the biphenyl ring with an azide, such as tributyltin azide. U.S. Pat. No. 5,270,317 discloses reaction times of up to 210 hours.
U.S. Pat. No. 5,629,331 also describes the synthesis of Irbesartan from the precursor 2-n-butyl-3-[(2′-cyanobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]non-1-en-4-one with sodium azide and triethylamine hydrochloride in an aprotic dipolar solvent, neutralisation of one of its alkaline salts in an aqueous medium and subsequent recrystallisation to obtain form A. The utilisation of azides involves safety risks, while aprotic dipolar solvents, such as N-methylpyrrolidone, have a relatively high boiling point and can be difficult to eliminate.
Patent WO 2004/065383 also describes the synthesis of Irbesartan tritylate by reacting 2-(1-trityl-1H-tetrazol-5-yl)phenylboronic acid with 2-butyl-3-(4′-bromobenzyl)-1,3-diazaspiro[4,4]non-1-en-4-one under Suzuki coupling conditions. The product so obtained is then submitted to acid conditions in order to hydrolyse the trityl group of the tetrazole ring in order to finally give Irbesartan. One negative aspect of said technique is the use of a voluminous protecting group such as trityl, which very considerably increases the molecular weight of the last synthesis intermediate, which last is then dramatically diminished in the final hydrolysis that provides Irbesartan, thereby resulting in a process of low atomic efficiency. This further creates a considerable amount of residual products and increases the number of synthesis steps in the process.
Patents DE4313747, DE4407488, U.S. Pat. No. 5,596,006, EP594022 and WO9609301 describe the synthesis of other biphenyl compounds by reacting an aryl halide with 2-(1H-tetrazol-5-yl)phenylboronic acid in the presence of a palladium catalyst.
A safe, ecological and high-yield method for obtaining Irbesartrán with few synthesis steps therefore remains necessary. Furthermore, it must be possible to apply said method on an industrial scale.